This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cytochrome P450 3A4 (CYP3A4) is the major zenobiotic- and drug-metabolizing human enzyme that is also involved in carcinogen activation. One of the areas significantly affected by the CYP3A4-mediated enzymatic transformations is development of anti-HIV drugs. To date, only a limited number of low-resolution x-ray structures of CYP3A4 complexes with substrates, drugs and inhibitors are available. To better understand the mechanism of CYP3A4 catalysis and inhibition, we obtained crystals of the enzyme bound to various substrates and inhibitors and aim to extend their resolution by collecting synchrotron data.